1. 黃其晟1 塗昭江1 張景年1 張偉嶠2 1天主教輔仁大學附設醫院 乳房外科 2台北醫學大學 藥學系
基因表現圖譜與功能性分析顯示乙一型整合素 (ITGB1)是三重陰性乳癌的潛在性預後標記 Gene expression profiling combined with functional analysis identify integrin beta1 (ITGB1) as a potential prognosis biomarker in triple negative breast cancer
黃其晟1 塗昭江1 張景年1 張偉嶠2
1天主教輔仁大學附設醫院 乳房外科 2台北醫學大學 藥學系

2. Introduction
Triple negative breast cancer (TNBC) accounts for approximately % of all types of breast cancer, and treatment is still limited.
This type of breast cancer shows a high risk of recurrence, visceral metastasis, a worse prognosis, and shorter distant metastasis-free survival.
Several studies have been reported that genetics factors are associated with breast cancer disease progression and patients' survival.

3. TNBC Migration Biomed Res Int. 2014;2014:536591
PIK3R3, ITGB1, ITGAL, and ITGA6 involved in the regulation of actin cytoskeleton

4. ITGB1, SOC Channel
High ITGB1 expression in ovarian, lung, colon, prostate cancer.
Regulate cell migration and invasion
Activating EMT process (in gall bladder cancer)
Targeted by miRNA 9-3p in claudin-low BC
Calcium regulates cell migration
Calcium influx through Store-operated calcium channel
STIM1 and Orai1
Physiol Rev. 2015;95:

5. Materials and methods
We combined Taiwanese microarray data from the GEO database and The Cancer Genome Atlas (TCGA) database to study the role of Integrin Beta1 (ITGB1) in TNBC.
Two triple negative breast cancer cell lines (MDA-MB-231; MDA- MB-468) were used to validate the functions of ITGB1.

6. Results
We found that a higher ITGB1 gene expression level was associated to lower survival. Silencing of ITGB1 inhibited TNBC cell migration, invasion and store-operated calcium influx.

7. Taiwanese BC
GSE53752
Early (stage I and II, n=37) vs. late (stage III and IV, n=14)

8. MDA-MB231 Cell Lines Transfected with SiControl and SiITGB1
qPCR for mRNA and Western blot for protein expression

9. MDA-MB231 Migration and Invasion
Wound healing assay
Migration calculated by ImageJ

10. MDA-MB231 Invasion Matrigel-coated transwell cell culture
Quantification of cell invasion by phase-contrast microscopy

11. Store-operated Calcium Channel
Thapsigargin to open the SOC channel

12. MDA-MB468 MDA-MB231: basal-B, highly invasive
MDA-MB468: basal-A, weakly invasive

13. TCGA TNBC

14. Discussion Knockdown of ITGB1 inhibits TNBC migration and invasion
Knockdown of ITGB1 reduces calcium influx through SOC channel
High ITGB1 correlated to lower survival in Taiwanese TNBC

15. Conclusion
Our study provided a potential candidate biomarker for breast cancer cells migration, invasion and TNBC patients' survival.